CHAPTER11 CELLCOMMUNICATION SectionA:AnOverviewofCellSignaling Cellsignalingevolvedearlyinthehistoryoflife 2.Communicatingcellsmaybeclosetogetherorfarapart 3.Thethreestagesofcellsignalingarereception,transduction,andresponse Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings Introduction ã Celltocell communication is absolutely essential for multicellular organisms • Cells must communicate to coordinate their activities • Communication between cells is also important for many unicellular organisms • Biologists have discovered some universal mechanisms of cellular regulation, involving the samesmallsetofcellưsignalingmechanisms ã Cellsmayreceiveavarietyofsignals,chemical signals,electromagneticsignals,andmechanical signals Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings 1.Cellsignalingevolvedearlyinthehistory oflife ã Onetopicofcellconversationissex • The yeast Saccharomyces cerevisiae, the yeast of bread, wine, and beer, identifies its mates by chemical signaling • There are two sexes, a and alpha, each of which secretes a specific signaling molecule, a factor and alpha factor respectively • These factors each bind to receptor proteins on the other matingtype Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Oncethematingfactors haveboundtothe receptors,thetwocells growtowardeachother andexperienceother cellularchanges ã Twooppositecellsfuse, ormate ã Thea/alphacellcontains thegenesofbothcells. Fig.11.1 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Theprocessbywhichasignalonacellssurfaceis convertedintoaspecificcellularresponseconsists of a series of steps called a signaltransduction pathway • The molecular details in both yeast and animal cells are strikingly similar, even though their last common ancestor was over a billion years ago • Signaling molecules evolved first in ancient prokaryotes and were then adopted for new uses by singlecelled eukaryotes and multicellular descendents Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Cellsignalinghasremainedimportantinthe microbialworld. ã Myxobacteria,soilưdwellingbacteria,usechemical signalstocommunicatenutrientavailability ã Whenfoodisscarce,cellssecreteasignaltoothercells leadingthemtoaggregateandformthickưwalledspores Fig.11.2 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings 2.Communicatingcellsmaybeclose togetherorfarapart ã Multicellularorganismsalsoreleasesignaling moleculesthattargetothercells ã Sometransmittingcellsreleaselocalregulatorsthat influencecellsinthelocalvicinity ã Paracrinesignalingoccurs whennumerouscellscan simultaneouslyreceiveand respondtogrowthfactors producedbyasinglecell intheirvicinity Fig.11.3a1 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings • In synaptic signaling, a nerve cell produces a neurotransmitter that diffuses to a single cell that is almost touching the sender • An electrical signal passing along the nerve cell triggers secretion of the neurotransmitter into the synapse. • Nerve signals can travel along a series of nerve cellswithoutunwanted responsesfromothercells Fig.11.3a2 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Plantsandanimalsusehormonestosignalat greaterdistances ã Inanimals,specializedendocrinecellsrelease hormonesintothecirculatorysystem,bywhichthey traveltotargetcellsin otherpartsofthebody ã Inplants,hormonesmay travelinvessels,butmore oftentravelfromcellto cellorbydiffusioninair Fig.11.3b Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Hormonesandlocalregulatorsrangewidelyinsize andtype ã Theplanthormoneethylene(C2H4),whichpromotes fruitripeningandregulatesgrowth,isahydrocarbon withonlysixatoms ã Insulin,whichregulatessugarlevelsinthebloodof mammals,isaproteinwiththousandsofatoms Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings • The Ca2+ concentration in the cytosol is typically much lower than that outside the cell, often by a factor of 10,000 or more • Various protein pumps transport Ca2+ outside the cell or inside the endoplasmic reticulum or other organelles Fig.11.14 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã BecausecytosolicCa2+issolow,smallchangesin theabsolutenumbersofionscausesarelatively largepercentagechangeinCa2+concentration ã Signalưtransductionpathwaystriggerthereleaseof Ca2+fromthecellsER ã Thepathwaysleadingtoreleaseinvolvestillother secondmessengers,diacylglycerol(DAG)and inositoltrisphosphate(IP3) ã Bothmoleculesareproducedbycleavageofcertain phospholipidsintheplasmamembrane Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã DAGandIP3arecreatedwhenaphospholipase cleavesamembranephospholipidPIP2 • Phospholipase may be activated by a G protein or by a tyrosinekinase receptor • IP3 activates a gatedcalcium channel, releasing Ca2+ Fig. 11.15 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • Calcium ions may activate a signaltransduction pathway directly • Alternatively, Ca2+ binds to the protein calmodulin • This protein is present at high levels in eukaryotes • When calmodulin is activated by Ca2+, calmodulin binds to other proteins, either activating or inactivating them • These other proteins are often protein kinases and phosphatases relay proteins in signaling pathways Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings CHAPTER 11 CELL COMMUNICATION Section D: Cellular Responses to Signals In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus 2. Elaborate pathways amplify and specify the cell’s response to signals Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings 1.Inresponsetoasignal,acellmay regulateactivitiesinthecytoplasmor transcriptioninthenucleus ã Ultimately,asignalưtransductionpathwayleadsto theregulationofoneormorecellularactivities ã Thismaybeachangeinanionchannelorachangeincell metabolism • For example, epinephrine helps regulate cellular energy metabolism by activating enzymes that catalyze the breakdown of glycogen. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • The stimulation of glycogen breakdown by epinephrine involves a Gproteinlinked receptor, a G Protein adenylylcyclase andcAMP,and severalprotein kinasesbefore glycogen phosphorylase isactivated Fig.11.16 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Other signaling pathways do not regulate the activity of enzymes but the synthesis of enzymes or other proteins • Activated receptors may act as transcription factors that turn specific genes on or off in the nucleus Fig.11.17 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings 2.Elaboratepathwaysamplifyandspecify thecellsresponsetosignals ã Signalingpathwayswithmultiplestepshavetwo benefits ã Theyamplifytheresponsetoasignal ã Theycontributetothespecificityoftheresponse ã Ateachcatalyticstepinacascade,thenumberof activatedproductsismuchgreaterthaninthe precedingstep ã Intheepinephrineưtriggeredpathway,bindingbyasmall numberofepinephrinemoleculescanleadtotherelease ofhundredsofmillionsofglucosemolecules Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings • Various types of cells may receive the same signal but produce very different responses • For example, epinephrine triggers liver or striated muscle cells to break down glycogen, but cardiac muscle cells are stimulated to contract, leading to a rapid heartbeat • These differences result from a basic observation: • Different kinds of cells have different collections of proteins Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings • The response of a particular cell to a signal depends on its particular collection of receptor proteins, relay proteins, and proteins needed to carry out the response Fig. 11.18 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Twocellsthatresponddifferentlytothesame signaldifferinoneormoreoftheproteinsthat handleandrespondtothesignal ã Asinglesignalmayfollowasinglepathwayinonecell buttriggerabranchedpathwayinanother ã Twopathwaysmayconvergetomodulateasingle response ã Branchingofpathwaysandinteractionsbetween pathwaysareimportantforregulatingand coordinatingacellsresponsetoincoming information Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Ratherthanrelyingondiffusionoflargerelay moleculeslikeproteins,manysignalpathwaysare linked together physically by scaffolding proteins • Scaffolding proteins may themselves be relay proteins to which several other relay proteins attach • This hardwiring enhances the speed and accuracy of signal transfer between cells Fig.11.19 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Theimportanceofrelayproteinsthatserveas branchorintersectionpointsisunderscoredwhen theseproteinsaredefectiveormissing ã TheinheriteddisorderWiskottưAldrichsyndrome (WAS)isduetotheabsenceofasinglerelayprotein ã It leads to abnormal bleeding, eczema, and a predisposition to infections and leukemia • The WAS protein interacts with the microfilaments of the cytoskeleton and several signaling pathways, including those that regulate immune cell proliferation • When the WAS protein is absent, the cytoskeleton is not properly organized and signaling pathways are disrupted Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã Asimportantasactivatingmechanismsare inactivatingmechanisms ã Foracelltoremainalertandcapableofrespondingto incomingsignals,eachmolecularchangeinitssignaling pathwaysmustlastonlyashorttime ã Ifsignalingpathwaycomponentsbecomelockedintoone state,theproperfunctionofthecellcanbedisrupted ã Bindingofsignalmoleculestoreceptorsmustbe reversible,allowingthereceptorstoreturntotheir inactivestatewhenthesignalisreleased ã Similarly,activatedsignals(cAMPandphosphorylated proteins)mustbeinactivatedbyappropriateenzymesto preparethecellforafreshsignal Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ... signal triggers a specific cellular activity Fig.? ?11. 5 Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings CHAPTER? ?11? ? CELL COMMUNICATION Section B: Signal Reception and the Initiation of ... neurotransmitters Fig .11. 6 Copyrightâ2002PearsonEducation,Inc.,publishingasBenjaminCummings ã TheGproteinactsasanonưoffswitch ã IfGDPisbound,theGproteinisinactive ã IfATPisbound,theGproteinisactive Fig .11. 7a... (e.g., estrogen receptors) Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings CHAPTER? ?11 CELL COMMUNICATION Section C: SignalTransduction Pathways Pathways relay signals from receptors to cellular responses